KeratolysisPhase 1/2NCT02863809
Vision Restoration With a Collagen Crosslinked Boston Keratoprosthesis Unit
A Phase 1/2 study testing Riboflavin, Dextran and UVA Light Source in people with Keratolysis, run by Joseph B. Ciolino, MD at 13 sites in United States.
Trial summary
This is a phase I/II prospective, randomized, multi-center, double-masked, vehicle-controlled clinical trial evaluating the safety and efficacy of corneal collagen cross-linking the keratoprosthesis carrier tissue in subjects who are candidates for high-risk keratoprosthesis implantation but because of a history of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Keratolysis
- What is being tested?
- Riboflavin, Dextran and UVA Light Source
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 13 sitesUnited States
- Study dates
- 15 Mar 2017to 31 Aug 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide written informed consent
- Willing and able to comply with study assessments for the full duration of the study
- Age ≥ 18 years
- Candidate for a Boston Keratoprosthesis / Cornea transplant
- In generally good stable overall health
- Patients with an eye at risk for a cornea sterile ulcer which includes:
- Autoimmune diseases (mucus membrane pemphigoid, Stevens-Johnson syndrome, systemic lupus erythematosis, rheumatoid arthritis, or other autoimmune diseases); OR
- History of previous sterile cornea ulceration requiring a cornea transplant
Who cannot join
- Age < 18 years
- Inability to provide written informed consent and comply with study assessments for the full duration of the study
- No or minimal tear production with evidence of keratinization of the bulbar conjunctiva
- Corneal or ocular surface infection within 30 days prior to study entry
- Ocular or periocular malignancy
- Inability to wear a contact lens due to lid abnormalities or shortened fornix
Show all 9Show fewer
- Signs of current infection, including fever and current treatment with antibiotics
- Pregnancy (positive pregnancy test) or lactating
- Participation in another simultaneous interventional medical investigation or trial
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
W.K. Kellogg Eye Center
Ann Arbor, Michigan, 48105
Wills Eye
Bala-Cynwyd, Pennsylvania, 19007
Wilmer Eye Institute
Baltimore, Maryland, 21287
Illinois Eye and Ear Infirmary
Chicago, Illinois, 60612
University Hospitals Eye Institute
Cleveland, Ohio, 44106
Cincinnati Eye Institute
Edgewood, Kentucky, 41017
Tauber Eye Center
Kansas City, Missouri, 64111
Wilford Hall Ambulatory Surgical Center (WHASC)
Lackland Air Force Base, Texas, 78236
The Jules Stein Eye Institute
Los Angeles, California, 90095-7003
Bascom Palmer eye Institute
Miami, Florida, 33136
David and Ilene Flaum Eye Institute, University of Rochester
New York, New York, 14642
UC Davis Health System Eye Center
Sacramento, California, 95817
Shiley Eye Institute, University of California, San Diego
San Diego, California, 92093
About this study
Official title: A Phase I/II Prospective, Randomized, Multicenter, Double-Masked, Vehicle-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Corneal Collagen Cross-Linking of Keratoprosthesis Carrier Tissue in High-Risk Keratoprosthesis Implantation
This is a phase I/II prospective, randomized, multi-center, double-masked, vehicle-controlled clinical trial evaluating the safety and efficacy of corneal collagen cross-linking the keratoprosthesis carrier tissue in subjects who are candidates for high-risk keratoprosthesis implantation but because of a history of corneal melts or autoimmune diseases are not candidate for a traditional corneal transplant.
Read the detailed description
The study is a multi-center, parallel, randomized, double-blinded study with subsequent follow-up period of two years. Eight-four subjects across twelve sites will be randomized 1:1 to receive either a corneal tissue that have been cross-linked or not cross-linked (No UVA light source). Cross-linking is a term that refers to the linking of polymers (long chain) molecules by chemical bonds. It is believed that cross-linking the cornea will make the cornea stronger and more resistant to degradation.
CorneaGen (formerly Keralink International) (Baltimore site) will supply the donor tissue and Avedro Inc (Waltham MA) will supply the riboflavin and the UV light source. Staff at CorneaGenwill administer the riboflavin with dextran solution and perform the cross-linking procedure according to one of randomization groups before shipping the masked donor cornea to study sites for Boston Keratoprosthesis (B-KPro) implantation.
- Conditions
- Keratolysis
- Being tested
- Riboflavin, Dextran, UVA Light Source
- Keywords
- Keratolysis, Corneal Melting, Boston KPro, Keratoprosthesis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RiboflavinDrug
Also called Vitamin B2
Riboflavin, a water soluble vitamin, is an essential nutrient and a natural component of many foods.
DextranDrug
Also called Dextran 70 6% in 0.9%, Sodium Chloride Dextran 70 6% in 5% Dextrose, Gentran 70, Hyskon
Dextran is used to increase the viscosity of the solution.
UVA Light SourceDevice
Also called KXL® System
Avedro's KXL® System is a UVA irradiation system that uses a light emitting diode (LED) to deliver a dose of UVA light to a targeted treatment area for illuminating the cornea during corneal collagen cross-linking.
| Study group | Role | What they receive |
|---|---|---|
| Active Treatment Arm | Experimental | De-epithelialized corneas cross-linked with riboflavin 0.1% and dextran 20% solution AND ultraviolet A light (UVA Light Source). Receives: Drug: Riboflavin; Drug: Dextran; Device: UVA Light Source |
| Control Treatment Arm | Active comparator | De-epithelialized corneas will be exposed to only riboflavin 0.1% with dextran 20% solution (NO ultraviolet A light). Receives: Drug: Riboflavin; Drug: Dextran |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time From Surgery to Device Loss or Replacement
If the device fails after surgery the time and reason behind the failure will be recorded. The number of device losses in the control group will be compared to the number of device losses in investigational group.
Measured: 2 years
Secondary outcomes (4)
Number of Participants With Kpro Retention at 12 Months
The number of participants that retained kpro devices at the end of twelve months will be studied and differences in retention rate between investigational and control groups will be reported
Measured: Twelve months
Number of Cumulative Delayed Epithelial Healing Events at Day 30
The number of incidences of delayed epithelial healing at day 30 will be recorded. If there is delayed epithelial healing at day 30 it will be determined if those incidences occurred more often in the control group versus the investigational group.
Measured: 30 days
Median Time From Surgery to Retroprosthetic Membrane Treatment in Days (Laser or Surgical Interventions)
If follow up surgery is needed to replace or treat the prosthetic the time and reason will be recorded and the number of incidences will be compared between the study treatment groups
Measured: 2 years
Median Time From Surgery to Occurrence of Vitritis (Sterile or Infectious)
The time (days) and number of incidences of vitritis will be recorded for the subject in which it occurred and the number of incidences will be compared between the study treatment groups.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2016 (estimated)
- Study start15 Mar 2017
- Primary completion30 Jun 2021
- Study completion31 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for KeratolysisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joseph B. Ciolino, MD
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor-investigator, Joseph B. Ciolino, MD, Massachusetts Eye and Ear Infirmary
- Investigators
- Joseph B. Ciolino, MD, Principal investigator, Massachusetts Eye and Ear Infirmary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02863809
- Sponsor's protocol ID
- 798474
- Status last verified
- Apr 2023
- First submitted
- 1 Jun 2016
- Last updated
- 10 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No: The data within StudyTrax will be extracted at the completion of the study. This data will be held in a secure network file at MEEI for at least two years following a marketing application submission to the FDA or longer, if required by the MEEI IRB.
Publications
Davis SA, Bovelle R, Han G, Kwagyan J. Corneal collagen cross-linking for bacterial infectious keratitis. Cochrane Database Syst Rev. 2020 Jun 17;6(6):CD013001. doi: 10.1002/14651858.CD013001.pub2.
PubMed 32557558
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Prospective, Randomized, Multicenter, Double-Masked, Vehicle-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Corneal Collagen Cross-Linking of Keratoprosthesis Carrier Tissue in High-Risk Keratoprosthesis Implantation
- ClinicalTrials.gov ID
- NCT02863809
- Acronym / sponsor ID
- 798474
- Conditions
- Keratolysis
- Keywords
- Keratolysis, Corneal Melting, Boston KPro, Keratoprosthesis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Joseph B. Ciolino, MDUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- 15 Mar 2017 (actual)
- Primary completion
- 30 Jun 2021 (actual)
- Study completion
- 31 Aug 2021 (actual)
- First posted
- 11 Aug 2016 (estimated)
- Results
- Posted 10 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase I/II prospective, randomized, multi-center, double-masked, vehicle-controlled clinical trial evaluating the safety and efficacy of corneal collagen cross-linking the keratoprosthesis carrier tissue in subjects who are candidates for high-risk keratoprosthesis implantation but because of a history of corneal melts or autoimmune diseases are not candidate for a traditional corneal transplant.
Detailed description
The study is a multi-center, parallel, randomized, double-blinded study with subsequent follow-up period of two years. Eight-four subjects across twelve sites will be randomized 1:1 to receive either a corneal tissue that have been cross-linked or not cross-linked (No UVA light source). Cross-linking is a term that refers to the linking of polymers (long chain) molecules by chemical bonds. It is believed that cross-linking the cornea will make the cornea stronger and more resistant to degradation.
CorneaGen (formerly Keralink International) (Baltimore site) will supply the donor tissue and Avedro Inc (Waltham MA) will supply the riboflavin and the UV light source. Staff at CorneaGenwill administer the riboflavin with dextran solution and perform the cross-linking procedure according to one of randomization groups before shipping the masked donor cornea to study sites for Boston Keratoprosthesis (B-KPro) implantation.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Treatment Arm | Experimental | Drug: Riboflavin, Drug: Dextran, Device: UVA Light SourceDe-epithelialized corneas cross-linked with riboflavin 0.1% and dextran 20% solution AND ultraviolet A light (UVA Light Source). |
| Control Treatment Arm | Active comparator | Drug: Riboflavin, Drug: DextranDe-epithelialized corneas will be exposed to only riboflavin 0.1% with dextran 20% solution (NO ultraviolet A light). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Willing and able to provide written informed consent
- Willing and able to comply with study assessments for the full duration of the study
- Age ≥ 18 years
- Candidate for a Boston Keratoprosthesis / Cornea transplant
- In generally good stable overall health
Key exclusion criteria (9 listed)
- Age < 18 years
- Inability to provide written informed consent and comply with study assessments for the full duration of the study
- No or minimal tear production with evidence of keratinization of the bulbar conjunctiva
- Corneal or ocular surface infection within 30 days prior to study entry
- Ocular or periocular malignancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RiboflavinAlso: Vitamin B2Riboflavin, a water soluble vitamin, is an essential nutrient and a natural component of many foods. | Drug | Active Treatment Arm, Control Treatment Arm |
| DextranAlso: Dextran 70 6% in 0.9%, Sodium Chloride Dextran 70 6% in 5% Dextrose, Gentran 70, HyskonDextran is used to increase the viscosity of the solution. | Drug | Active Treatment Arm, Control Treatment Arm |
| UVA Light SourceAlso: KXL® SystemAvedro's KXL® System is a UVA irradiation system that uses a light emitting diode (LED) to deliver a dose of UVA light to a targeted treatment area for illuminating the cornea during corneal collagen cross-linking. | Device | Active Treatment Arm |
Primary outcome
Time From Surgery to Device Loss or Replacement
Time frame: 2 years
If the device fails after surgery the time and reason behind the failure will be recorded. The number of device losses in the control group will be compared to the number of device losses in investigational group.
4 secondary outcomes
Number of Participants With Kpro Retention at 12 Months
Time frame: Twelve months
Number of Cumulative Delayed Epithelial Healing Events at Day 30
Time frame: 30 days
Median Time From Surgery to Retroprosthetic Membrane Treatment in Days (Laser or Surgical Interventions)
Time frame: 2 years
Median Time From Surgery to Occurrence of Vitritis (Sterile or Infectious)
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32557558Davis SA, Bovelle R, Han G, Kwagyan J. Corneal collagen cross-linking for bacterial infectious keratitis. Cochrane Database Syst Rev. 2020 Jun 17;6(6):CD013001. doi: 10.1002/14651858.CD013001.pub2.
- Individual participant dataSharing planned: No. The data within StudyTrax will be extracted at the completion of the study. This data will be held in a secure network file at MEEI for at least two years following a marketing application submission to the FDA or longer, if required by the MEEI IRB.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph B. Ciolino, MD principal investigator
Massachusetts Eye and Ear Infirmary
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Riboflavin, Dextran and UVA Light Source in people with Keratolysis, run by Joseph B. Ciolino, MD at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time From Surgery to Device Loss or Replacement (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02863809, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2023.